Paisley was born on October 28, 1972, in Glen Dale, West Virginia. He is the only child of Douglas Edward "Doug" Paisley, who worked for the West Virginia Department of Transportation, and Sandra Jean "Sandy" (née Jarvis) Paisley, a Teacher. He was raised in Glen Dale, West Virginia. He has stated that his love of country music stems from his maternal grandfather, Warren Jarvis, who gave him his first guitar, a Sears Danelectro Silvertone, and taught him how to play at eight years old. At ten, he performed for the first time in public by singing in his church. He later recalled that, "Pretty soon, I was performing at every Christmas party and Mother's Day event. The neat thing about a small town is that when you want to be an Artist, by golly, they'll make you one." At age 13, he wrote his first song, "Born on Christmas Day", which later appeared on his album Brad Paisley Christmas. He had been taking lessons with local Guitarist Clarence "Hank" Goddard. By 13, Goddard and Paisley formed a band called "Brad Paisley and the C-Notes", with the addition of two of Paisley's adult friends.

Paisley graduated from John Marshall High School in Glen Dale, West Virginia, in 1991, and then studied for two years at West Liberty State College in West Liberty, West Virginia. He was awarded a fully paid ASCAP scholarship to Belmont University in Nashville, Tennessee, where he majored in music Business and received a Bachelor of Business Administration degree from the Mike Curb School of Music Business in 1995. He interned at ASCAP, Atlantic Records, and the Fitzgerald-Hartley management firm. While in college, he met Frank Rogers, a fellow student who went on to serve as his Producer. Paisley also met Kelley Lovelace, who became his songwriting partner. He also met Chris DuBois in college, and he, too, would write songs for him.

He is also a lifelong fan of the Cleveland Browns. Paisley sang the national anthem before a game during the 1999 season, and stated in an interview with ESPN his dream job would be to play football for them. He also invited former Browns Quarterback Brady Quinn to a concert at the Blossom Music Center, in 2008.

In the last months of 2000, Paisley had a relationship with fellow country music singer Chely Wright. Unbeknownst to Paisley, Wright and her female partner had moved together into a new home earlier in the year. In her autobiography, Wright expressed distress for how she treated him.

Later in 2000, Paisley won the Country Music Association's (CMA) Horizon Award and the Academy of Country Music's best new male vocalist trophy. He received his first Grammy Award nomination a year later for Best New Artist. On February 17, 2001, Paisley was inducted into the Grand Ole Opry. He was 28 when he accepted the invitation, and was the youngest member ever to join. PBS did a 75th anniversary concert special, in which Paisley and Chely Wright sang a song that they co-wrote called "Hard to Be a Husband, Hard to Be a Wife". This song later appeared on the compilation album Grand Ole Opry 75th Anniversary, Vol. 2. The concert would get a CMA nomination for Vocal Event of the Year. Paisley would later contribute to Wright's 2001 album Never Love You Enough, co-writing the tracks "One Night in Las Vegas", "Horoscope", and "Not as In Love". Paisley co-produced the former two tracks with her, in addition to playing guitar on them and featuring members of his road band, The Drama Kings; he also sang backing vocals on "One Night in Las Vegas" and "Not as In Love".

In 2002, he won the CMA Music Video of the Year for "I'm Gonna Miss Her (The Fishin' Song)". Several celebrities made notable guest appearances in the video, including Little Jimmy Dickens, Kimberly Williams, Dan Patrick, and Jerry Springer. His three other singles off the Part II album, "I Wish You'd Stay", "Wrapped Around", and "Two People Fell in Love", which all charted in the top 10. The album stayed in the charts for more than 70 weeks and was certified platinum in August 2002. To support his album, he toured the country as the opening act for Lonestar.

Paisley and Actress Kimberly Williams began dating in 2001. Paisley had first seen Williams in Father of the Bride. Paisley has stated that he watched Williams' performance and thought "She seems like a great girl — smart and funny and all those things that are so hard to find." In 2002, Williams appeared in a video for the song "I'm Gonna Miss Her (The Fishin' Song)", the last release from his Part II album. The two married on March 15, 2003, at Stauffer Chapel on the campus of Pepperdine University after a nine-month engagement. They live in Franklin, Tennessee, and had another home in Pacific Palisades that was sold in 2013.

Paisley is an active Freemason, a member of Hiram Lodge #7 in Franklin, Tennessee. Paisley is a member of the Southern Jurisdiction of the Scottish Rite of Freemasonry, and a Noble of the AAONMS, also known as Shriners. He was accompanied by his father, Doug Paisley (33º), for the ceremony on October 28, 2006, and has done a number of recordings supporting the virtues of Freemasonry and DeMolay International.

Paisley and Williams' first son, william Huckleberry, or "Huck", was born on February 22, 2007, in Nashville. Their second son, Jasper Warren (named after his grandfather, who bought Paisley his first guitar), was born on April 17, 2009.

A sixth instrumental album, titled Play, was released on November 4, 2008. Paisley and Keith Urban released to country radio their first duet together on September 8, 2008, "Start a Band". It was the first and only single from Play, and it went on to become Paisley's thirteenth number one hit and his ninth in a row. The album also features collaborations with James Burton, Little Jimmy Dickens, Vince Gill, John Jorgenson, B.B. King, Albert Lee, Brent Mason, Buck Owens, Redd Volkaert and Steve Wariner. Paisley and Urban both received Entertainer of the Year nominations from the CMA on September 10, 2008. On November 12, 2008, Paisley won Male Vocalist of the Year and Music Video of the Year for "Waitin' on a Woman" during the CMAs.

In late 2009, it was announced in Variety that Paisley would enter the world of scripted television as an executive Producer of a new hour-long drama series for The CW network called, appropriately, Nashville. The plot was written and created by Neal Dodson and actor Matt Bomer. The creator of the series One Tree Hill, Mark Schwahn directed the pilot and was to oversee the series had it been picked up. Actor Zachary Quinto is also an executive Producer on the series, along with Dodson, Bomer, and Corey Moosa. The pilot was not picked up for a series when The CW's fall schedule was announced in May 2010. The CW project is completely unrelated to the current ABC series, also named Nashville, even though his wife had a long-running recurring role in it and he has made two cameo appearances himself.

In 2010, Paisley and Wampler Pedals released the Brad Paisley signature Paisley Drive, a guitar overdrive pedal designed to his specifications. Paisley has also used Audiotech Guitar Products ABY Selector's for controlling his wireless receiver units.

Paisley released his book Diary of a Player: How My Musical Heroes Made a Guitar Man Out of Me in 2011 under Howard Books Publishing. He co-wrote the book with author David Wild, a contributing Editor for Rolling Stone magazine and an Emmy nominated TV Writer and Producer. The book is an autobiography and talks about Paisley's introduction to the music industry and how the events in his life helped to prepare him for what was up ahead. The book features topics such as the first guitar that his grandfather gave him, his first band the C-notes, the first song he wrote, and many more music/guitar related topics. Although the book does speak briefly of his personal life, the main focus is on his music and the start of his career.

On September 20, 2012, Paisley released a new single, "Southern Comfort Zone". The song debuted at number 25 on the Hot Country Songs chart, becoming Paisley's highest debut to date. It reached number 2 on the Country Airplay chart in 2013. The song was the first single from his ninth studio album, Wheelhouse, released on April 9, 2013.

On June 12, 2013, Paisley announced on his Twitter page that he would join the Rolling Stones onstage during the band's concert in Philadelphia.

Paisley is also a fan of West Virginia athletics and the Chicago Cubs. In 2014, Paisley appeared as a Celebrity guest picker on the popular ESPN show College Gameday, when it was held on the campus of West Virginia University.

In 2015 Santa Cruz Guitar Company introduced the Brad Paisley Signature Model, B/PW, acoustic dreadnought guitar. Paisley is often seen playing this model of guitar, such as in the 2017 Netflix original Brad Paisley's Comedy Rodeo.

In 2016 Paisley and Dr. Z Amplification collaborated and released the DB4 model. The name DB4 is thus named because it is "Doc & Brad's fourth amp design". The pentode preamp tube is a 5879 with EL84 output tubes.